Tumor necrosis serum (TNS) containing anti-tumor factors of undetermined nature induces a subpopulation of NK cells which is characterized by the newly discovered cell surface marker Qa5. Interferon (IF) does also induce Qa5 ion NK cells, as does concanavalin A (Con A) and bacterial lipopolysaccharide (LPS). The latter lymphocyte mitogens require T cells (Con A) or B cells (LPS) as cellular mediators, in contrast to IF or TNS which appears to activate NK cells directly. We will investigate the relationship between the immune system and NK cell activation and determine whether T cell-, B cell- and TNS-dependent activation of NK cells is mediated by interferon. This study will include experiments with autoimmune mice which we found to be NK cell deficient. The involvement of Qa5 ion NK cells in TNS-induced tumor regression will be investigated.